Project Summary/Abstract Impact: This research explores the premise that e-cig users are able to compensate for lower nicotine products by adapting their behavior to maintain their desired nicotine level. When presented with a lower nicotine product, nicotine addicted e-cig users may alter their puffing topography to generate a more highly dense aerosol, and thus increase their consumption of total particulate matter in order to achieve their dose of nicotine. In addition, users may alter their respiratory parameters such as increasing inhalation volume, pulling the aerosol deeper into the lung and increasing the surface area available for gas exchange, or holding the aerosol in their lungs for a longer period of time, allowing for more nicotine uptake before exhaling. All of these changes in behavior are considered compensation, and may result in increased exposure to total particulate matter and ultimately increase the harm potential of what would otherwise be consider a reduced harm product. Study Design: The project involves a 17-day natural environment study with a two arm, two period cross-over design. N=80 current established adult vape pen users, currently using eliquids with nicotine strengths greater than or equal to 13 mg/mL, with no intention to quit e-cig use, and no use of combustible or other tobacco products will be randomized by age, gender, usual brand nicotine strength, and nicotine dependence score into control (non-switching) and test (switching) arms. The test arm will be switched to a lower nicotine strength eliquid (6 mg/mL) matching their usual flavor, while the control arm will continue to use their usual nicotine strength. The RIT wPUMTM vape pen monitor will record puff topography (puff volume, flow rate, duration, interpuff interval) and the Hexoskin wearable sensorized garment will record respiratory parameters (inhalation/exhalation volume and time, breath hold) for every puff taken while vaping ad-lib in their natural environment. Participants will provide salivary cotinine samples and complete a daily log of product use, compliance and subjective effects including craving, withdrawal symptoms and positive/negative emotional state on users? ability to compensate for low nicotine eliquids. Specific Aims: The objective of Aim 1 is to quantify changes in topography, respiration and TPM exposure upon switching from their usual to a lower nicotine strength eliquid. The objective of Aim 2 is to assess the extent to which users are able to compensate their behavior using salivary cotinine levels before and after the switch as a proxy for compensation efficacy. We will test two hypotheses; (H1) exposure to TPM will increase upon switching to a reduced nicotine eliquid and (H2) salivary cotinine levels will remain unchanged. We will investigate the presence of random subjective effects, and age/gender on compensation using a generalized linear mixed-effects model. Regulation: Knowledge gained informs regulations related to limiting nicotine in eliquids. Exposure to both nicotine and total particulate matter are important in risk assessment, and the potential to inadvertently increase one by decreasing the other must be considered in product regulation.